Many insulin-dependent diabetic (IDDM) adolescents have elevated growth hormone (GH) and low insulin-like growth factor-I (IGF-I) levels. These hormonal abnormalities contribute to insulin-resistance and further exacerbate already compromised mechanisms of fuel homeostasis. This study compared baseline IGF and IGF binding protein (IGFBP) levels and responses to treatment with recombinant IGF-I in normal and diabetic male adolescents. Subjects were studied before and after daily 10 hour subcutaneous infusions of saline or IGF-I (20 micrograms/kg/hour). Baseline IGF-I levels were almost 50% lower and IGF-II levels were significantly higher in diabetics compared to controls. IGF-I infusion produced an increase of 3-4 fold in serum IGF-I levels and a profound reduction in IGF-II levels. IGFBP1 levels increased dramatically in diabetics and modestly in normals during two days of IGF-I infusion but IGFBP3 levels were not affected. Spontaneous overnight and arginine- stimulated GH secretion were suppressed by approximately 50% in both groups following IGF-I infusion. Insulin requirements were substantially reduced in diabetics receiving IGF-I and insulin secretion was suppressed in normals, with no evidence of a change in insulin half-life. No hypoglycemia or other adverse effect occurred during IGF-I treatment. These findings suggest that treatment of adolescent diabetics with IGF-I in addition to insulin may achieve better metabolic and anabolic balance than treatment with insulin alone. Long-term studies are now required to determine if these effects are sustained and to evaluate the effects of normalizing IGF-I and GH levels on growth and on diabetic complications.